Both incidence and mortality from melanoma continue to rise in the United States. In 1992, the projected annual incidence and mortality from melanoma were 32,000 and 6,700, respectively.[1] By 2004, these figures had increased to 55,100 and 7,910, respectively.[2] The lifetime risk of developing melanoma was only 1:1500 in 1935, but had reached 1:75 in 2000.[3] The mortality rate due to melanoma correlates with advancing stage, which is determined by thickness and ulceration of the primary lesion, presence of regional lymph node (LN) metastasis or distant metastasis.[4] There is no adequately proven treatment for metastatic melanoma. Localized cutaneous melanoma is often curable by surgery alone, yet once lymph node metastasis occurs (which marks the beginning of AJCC (American Joint Committee on Cancer) stage III disease), likelihood of systemic disease and mortality increase. Whereas the estimated 10-year survival-rate for stage II melanoma patients is approximately 55%, that of stage III melanoma patients is only about 35%.[5]
Regional LN status is the single most important prognostic factor in melanoma. Patients with regional LN metastasis (AJCC stage III disease) have worse prognosis than those without (AJCC stage I/II), even if they have the same Breslow thickness.[5] Among the AJCC stage 1V patients, the patients with no history of intervening stage III disease (no history of regional lymph node metastasis) have significantly better prognosis than those with history of intervening stage III disease (history of regional lymph node metastasis).[6] These findings suggest that lymph node metastasis is not just a passive event dependent on time, but rather an active event based upon differential metastatic potential among different primary lesions. Furthermore, ability of melanoma to metastasize to regional lymph nodes is an independent measure of overall aggressive potential. Therefore, identification of factors associated with, if not causative of, regional lymph node metastasis is a crucial step in understanding pathophysiology of regional and possibly distant metastasis.